Cardio-Immuno-Oncology

he burgeoning field of cardio-oncology is continuing to grow in step with major scientific developments in oncology that have improved cancer prognosis and survivorship.Once focused primarily on addressing the effects of conventional chemotherapy, cardio-oncology is now increasingly defining itself in relation to acute and chronic cardiovascular and metabolic risks of targeted oncologic therapies.1 In a bidirectional interaction, cardio-oncology holds the potential for bridging the application of fundamental molecular advances from hematology and oncology in the cardiovascular field.These concepts are now amalgamating in cardio-immuno-oncology or the cardiovascular sequelae of cancer therapies modulating the immune system.Drugs that modulate the immune system have emerged as important treatments for many human diseases ranging from autoimmune diseases to cancer.What started with biologics in rheumatology for the modulation of cytokines has extended to unprecedented proportions in cancer therapy.Immunotherapies in oncology include cytokines, antibodies directed against cancer antigens and cellbased therapies.Perhaps most impactful in the current anticancer therapeutic armamentarium are immune checkpoint inhibitors (ICI), antibodies targeting brakes or checkpoints in immune cells, including T lymphocytes.ICI have been effective in several previously deadly cancers, such as melanoma and lung cancer, and are now being tested, often in combination, in virtually every cancer type.Seven ICI have been approved.Between 2011 and 2018, the percentage of patients with cancer who are eligible for ICI therapy increased from 1.54% to 46.6%.The overall landscape of immuno-oncology is staggering.As of September 2017, there were 940 immuno-oncology agents in clinical development owned by 462 different companies or academic institutes, with another 1064 compounds in the preclinical phase. 2 At the same time, there were 3042 active clinical trials evaluating efficacy in nearly 600 000 patients. 2 It is estimated that >50% of research and development in pharmaceutical companies is now focused on immuno-oncology.Although immunotherapies can lead to cure in a subset of patients with cancer, they can also result in immune-related side effects.Cell-based therapies (eg, chimeric antigen receptor T-cell therapy) can lead to a cytokine release syndrome.ICIassociated cardiac complications include myocarditis, pericarditis, vasculitis, and arrhythmias, and can occur in 1% of treated patients.3 Among the immune-related side effects induced by ICI, cardiovascular inflammatory complications have been the most challenging to recognize and treat.For example, ICI-associated myocarditis can be difficult to diagnose because of its unusual presentation (electrocardiographic instability rather than heart failure) and has proven hard to treat (≈50% mortality).3 It is conceivable that severe, acute ICI-associated myocarditis represents only the tip of the iceberg, with lower intensity, chronic cardiovascular effects also occurring, but less well characterized.